The aim is to investigate the molecular biology of tumor metastasis and invasion. We are using a variety of techniques to identify specific genetic elements whose expression is altered in metastatic cells. Pulse-labeling studies of paired nonmetastatic metastatic cells revealed differences in the synthesis of specific proteins. RNA from cultured cell lines and tissues with varying metastatic potential have been analyzed by cell-free translation in a rabbit reticulocyte lysate and by hybridization analysis. In vitro translation studies indicated that the levels of several specific mRNAs are either markedly increased or decreased in metastatic murine melanoma cells. A cDNA library of the murine melanoma cells was constructed. Approximately 40,000 clones of the recombinant DNA library were screened to isolate specific genes involved in the etiology and maintenance of the neoplastic state. To date, we have isolated several molecular clones which code for mRNAs which are expressed to a differential degree in metastatic versus nonmetastatic lines. In addition, levels of mRNA for the major excreted protein (MEP) of transformed murine cells are increased in the nonmetastatic cells. In contrast, levels of mRNA for type IV collagen are increased in the metastatic cells.